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Laser Photocoagulation and, to a Lesser Extent, Photodynamic Therapy Target and Enhance Adenovirus Vector–Mediated Gene Transfer in the Rat Retina

¹From the Department of Ophthalmology, Saitama Medical School, Saitama, Japan; the ²Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland; and ³GenVec Inc., Gaithersburg, Maryland.

PURPOSE. To evaluate the transduction efficiency and localization of a reporter gene after intravitreous injection of adenovirus vector in laser photocoagulation (PC)- and photodynamic therapy (PDT)–treated eyes.

METHODS. Adult Lewis rats received fundus PC, fundus PDT, or no treatment. Intravitreous injection of an adenovirus vector containing the construct expressing ß-galactosidase (AdlacZ.11D) was performed in each group. All eyes were then enucleated for histochemistry and processed for quantitative image analysis.

RESULTS. In eyes with no treatment, there was moderate to intense staining for lacZ in the anterior segment, but little in the retina. In eyes treated with PC and PDT, there was significantly more LacZ staining in the retina. The increased staining corresponded closely with the sites treated with PC and PDT. Gene transduction in PC-treated eyes was enhanced and extended to at least 135 days after virus delivery, but not extended in PDT-treated eyes. Gene transfer and expression were targeted and enhanced at the site of laser burns, at all doses tested (3 x 10⁵ to 3 x 10⁹ particles per eye).

CONCLUSIONS. Compared with untreated eyes, eyes treated with PC and to a lesser extent PDT, manifest increased transduction efficiency, in areas of the retina that are targeted by laser treatment. This finding suggests a new and promising strategy for the treatment of retinochoroidal neovascularization. Adenovirus gene therapy in combination with PC or PDT would have the advantage of increased transduction efficiency; increased duration of transgene expression; targeted delivery; and, potentially, a lower effective dose of virus.